Epithelial tubule interconnection driven by HGF-Met signaling in the kidney DOI Creative Commons
Isabel López‐García,

Sunhee Oh,

Christopher Chaney

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(52)

Published: Dec. 20, 2024

The formation of functional epithelial tubules is critical for the development and maintenance many organ systems. While mechanisms tubule by cells are well studied, process anastomosis—where connect to form a continuous network—remains poorly understood. In this study, we utilized single-cell RNA sequencing analyze embryonic mouse kidney undergoing anastomosis. Our analysis identified hepatocyte growth factor (HGF) as key potential mediator process. To investigate further, developed an assay using spheroids with fluorescently tagged apical surfaces, allowing us visualize quantify tubule–tubule connections. results demonstrate that HGF promotes anastomosis, it does so through MAPK signaling pathway MMPs, independently cell proliferation. Remarkably, treatment collagenase was sufficient induce anastomosis in kidneys. These findings provide foundational understanding how enhance tubular networks. This has significant clinical implications use vitro–grown tissues transplant medicine, potentially improving success integration transplanted tissues.

Language: Английский

Mouse embryonic kidney transplantation identifies maturation defects in the medulla DOI Creative Commons

Hiroshi Ide,

Koichiro Miike,

Tomoko Ohmori

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 5, 2024

Kidney organoids are connected to the host circulation and mature after transplantation. However, they still immature compared adult kidneys, their precise maturation stages remain unclear. By transplanting mouse embryonic kidney as a model system for organoid transplantation, we report here defects of graft, especially in medulla. Single cell profiling developing kidneys vivo identified gene sets associated with collecting duct epithelium medullary stroma. These data revealed an upregulation genes channel/transporter functions immune defense, well downregulation neuronal genes. Using these marker genes, found that stroma grafts barely corresponds perinatal stage, which was confirmed histologically by using representative Thus, obtained serve coordinates renal medulla will be helpful analyzing its They also provide useful basis further transplanted organoids.

Language: Английский

Citations

0
Epithelial tubule interconnection driven by HGF-Met signaling in the kidney DOI Creative Commons
Isabel López‐García,

Sunhee Oh,

Christopher Chaney

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(52)

Published: Dec. 20, 2024

The formation of functional epithelial tubules is critical for the development and maintenance many organ systems. While mechanisms tubule by cells are well studied, process anastomosis—where connect to form a continuous network—remains poorly understood. In this study, we utilized single-cell RNA sequencing analyze embryonic mouse kidney undergoing anastomosis. Our analysis identified hepatocyte growth factor (HGF) as key potential mediator process. To investigate further, developed an assay using spheroids with fluorescently tagged apical surfaces, allowing us visualize quantify tubule–tubule connections. results demonstrate that HGF promotes anastomosis, it does so through MAPK signaling pathway MMPs, independently cell proliferation. Remarkably, treatment collagenase was sufficient induce anastomosis in kidneys. These findings provide foundational understanding how enhance tubular networks. This has significant clinical implications use vitro–grown tissues transplant medicine, potentially improving success integration transplanted tissues.

Language: Английский

Citations

0